Opportunistic infections are a major cause of morbidity and mortality of AIDS patients in developing countries and AIDS patients are susceptible to a number of cancers caused by opportunistic infections. Kaposi's Sarcoma (KS) is the most common tumor of AIDS patients and is the most commonly reported tumor overall in parts of Africa. The etiologic agent of KS is Kaposi's Sarcoma-associated herpesvirus (KSHV or HHV-8). KSHV is invariably found in the main KS tumor cell, the spindle cell, a cell of endothelial origin and is predominantly found in th latent state. There are no drugs to target latent infection of herpesviruses. Therefore, an important therapeutic approach is to delineate and target host endothelial cell processes required for KSHV latency. Recent studies have shown that pathologic changes in cell metabolism can be a driver of oncogenesis rather than simply an adaptation to the tumor environment. While a few studies have examined alterations of cellular metabolism during lytic infection of viruses, we were the first to examine changes in cellular metabolism during latent infection. We demonstrated that latent KSHV infection of endothelial cells leads to an alteration in glucose carbon utilization, specifically inducing aerobic glycolysis. Importantly, we found that KSHV induction of aerobic glycolysis is essential for the survival of latently infected cells. Our preliminary data for this proposal show that latent KSHV infection also induces glutamine uptake and requires glutamine for the survival of latently infected cells. Therefore, altered utilization f both glucose and glutamine, are critical for the maintenance of KSHV latency. In this proposal, we will examine how glucose and glutamine are utilized specifically in endothelial cells latently infected with KSHV, the relevant cell type for KS tumors. In the first aim we will analyze glucose metabolism during latent infection to further identify how glucose carbons are metabolized and why these alterations are needed for the survival of latent infection. We will also examine the cellular and viral mechanisms for induction of altered glucose utilization. In the second aim we will analyze the cellular and viral mechanism of increased glutamine uptake and determine how glutamine is metabolized during latent infection. Our data indicate that pathologic changes in cellular metabolism induced by KSHV could provide novel therapeutic targets for latently infected cells and would ultimately provide therapeutic targets for KS tumors in AIDS patients.